新型多氮杂环双功能螯合剂的研发及在Al18F标记中的应用研究

PET is one of the most successful molecular imaging technology. 18F is widely used for PET imaging with excellent properties such as short half-life and the high positron energy. However, the current time-consuming, multiple-step synthetic procedures hinder the development and widespread use of the novel tracers in clinic. Simplifying the 18F-labaling process has become the focus in the area of radiopharmaceuticals. Application of bifunctional chelating agents coordinating to 18F fluoride−aluminum provides a new strategy . In this project, we intend to design and synthesis novel bifunctional chelating agents. The labeling processes were optimized, and the relationship among electronic, steric effects of the chelating agents and Al18F labeling efficiency were also investigated. The biological characters of novel bifunctional chelating agents conjugated RGD dimer PET probes labeled with Al18F were evaluated through in vitro cells study and in vivo microPET imaging etc. Some objectives for example simplifying process, improving labeling yield, shortening time and not affecting the targeting vector etc were also guarantied in the study. The achivements will extend the types of bifunctional chelating agents, simplify the process of 18F labeling and be benefit to spread of PET imaging agents in clinic.

PET显像是目前临床上最成熟的分子影像技术，18F是临床广泛使用的正电子核素，具有半衰期短，射线能量高等特点。但现有18F标记工艺条件苛刻、繁琐、费时，限制了PET显像剂的临床推广，简化标记工艺成为放射性药物领域的重中之重。氟化铝标记新策略有望解决此难题，利用双功能螯合剂与Al18F配位这一新策略可极大简化18F标记工艺。本项目拟设计、合成新型双功能螯合剂，研究螯合剂的电子效应、空间位阻效应与Al18F标记效率的关系，优化18F标记工艺；并以RGD二聚体为载体，通过体外细胞实验、活体microPET显像考察采用新型双功能螯合剂偶联制得的18F-RGD PET探针的生物活性，力求标记工艺简捷，产率高，耗时短，且不影响载体的靶向性。本项目若成功，将拓展双功能螯合剂的种类，简化18F标记工艺，对于PET显像剂在临床的推广至关重要。

PET显像是目前临床上最成熟的分子影像技术，18F是临床广泛使用的正电子核素，具有半衰期短，射线能量高等特点。但现有18F标记工艺条件苛刻、繁琐、费时，限制了PET显像剂的临床推广，简化标记工艺成为放射性药物领域的重中之重。氟化铝标记新策略有望解决此难题，利用双功能螯合剂与Al18F配位这一新策略可极大简化18F标记工艺。本项目设计、合成了新型双功能螯合剂，优化18F标记工艺；并以MATBBN、IF7和GGGRDN-IF7为载体，通过体外细胞实验、活体microPET显像考察正电子探针的生物活性。本项目拓展双功能螯合剂的种类，简化18F标记工艺，对于PET显像剂在临床的推广至关重要。